(Chest. 2005;128:704-708.)
© 2005
American College of Chest Physicians
Transbronchial Needle Aspiration in the Diagnosis of Endobronchial Malignant Lesions*
A 3-Year Experience
Benan Caglayan, MD;
Ulku Aka Akturk, MD;
Ali Fidan, MD;
Banu Salepci, MD;
Sevda Ozdogan, MD;
Gülsen Sarac, MD and
Elif Torun, MD
* From the Department of Chest Diseases, Kartal Education and Research Hospital, Istanbul, Turkey.
Correspondence to: Benan Caglayan, MD, Tellikavak Sok, Selahattin Bey Apt 22/3, Da 13, 34738 Erenkoy, Istanbul, Turkey; e-mail: benancag{at}ttnet.net.tr
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Abstract
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Study objectives: To establish the diagnostic yield of transbronchial needle aspiration (TBNA) and its contribution to conventional diagnostic techniques (CDT) such as forceps biopsy, bronchial washing, and bronchial brushing in the diagnosis of malignant endobronchial lesions.
Design: Retrospective clinical study.
Patients: One hundred fifteen lung cancer patients
Measurement and results: We reviewed files of 115 lung carcinoma cases diagnosed in our clinic from 2001 to 2003 with endobronchial lesions sampled by CDT and TBNA. The lesions were classified into three groups: exophitic mass lesion (EML), submucosal disease, and peribronchial disease. The diagnostic yield of TBNA and CDT was compared to that of the combination of CDT and TBNA with respect to the type and location of the lesion and the histopathologic subgroups. Of the 115 cases, histology findings were confirmed by TBNA in 91 cases (79%), CDT in 75 cases (65%), and TBNA plus CDT in 105 cases (91%). The difference of the diagnostic yield of CDT vs TBNA plus CDT was statistically significant (p < 0.001). In peribronchial disease, the sensitivity of TBNA plus CDT was significantly better than CDT (87% vs 52%, p < 0.001). In EML and submucosal disease, addition of TBNA to CDT improved sensitivity from 85 to 100% and from 84 to 97%, respectively (p > 0.05). Regarding localization, the addition of TBNA to CDT increased sensitivity in the trachea and main bronchi, and in right upper and middle lobe lesions (p < 0.05). By the addition of TBNA to CDT, small cell lung cancer and non-small cell lung cancer cases demonstrated improvements in sensitivity from 74 to 100% and 61 to 87%, respectively. This significant difference (p < 0.05) was attributed to the peribronchial disease group.
Conclusion: In the case of peribronchial disease, the addition of TBNA to CDT improves the diagnostic yield of the bronchoscopic examination.
Key Words: bronchoscopy diagnostic yield endobronchial lesion endobronchial malignancy endobronchial needle aspiration fiberoptic bronchoscopy lung cancer transbronchial needle aspiration
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Introduction
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Transbronchial needle aspiration (TBNA) is a beneficial, safe, and minimally invasive bronchoscopic technique used in the diagnosis and staging of bronchogenic carcinoma. It was first introduced by Wang et al in the late 1970s. This method is usually performed through a flexible bronchoscope and provides cytologic or histologic sampling of mediastinal lesions that lie adjacent to the tracheobronchial tree.1234 Previously, the utility of TBNA was restricted to mediastinal lymph node and extrabronchial lesion sampling. Its use has been expanded to complement conventional diagnostic techniques (CDT) such as bronchial washing (BW), bronchial brushing (BB), and forceps biopsy (FB) in the diagnosis of lung cancer with endobronchial lesions.45
Central bronchogenic carcinoma tends to manifest in one of three patterns. The growth may be predominantly in the mucosal layer, in which case the tumor presents as a bulky, exophytic mass. It can also spread predominantly in the submucosa, with endoscopic findings consisting of erythema, loss of the normal bronchial markings, narrowing of the bronchus, or thickening of the mucosa. The third pattern is that of a predominantly peribronchial spread, in which the endoscopic findings are usually narrowing of the airway due to extrinsic compression of the bronchus.6 Particularly in the presence of peribronchial and submucosal lesions, diagnosis with CDT such as BW, BB, and FB is more difficult. However, applying a needle into the lesion provides access to lower layers of the bronchus and adjacent lesions. Despite its advantages in diagnosis, TBNA is still an underutilized procedure in many centers because of the risk of damage to the bronchoscope, need for experienced staff, and high cost.1 This is a retrospective study carried out in our clinic to investigate the diagnostic yield of TBNA and its contribution to CDT in lung cancer patients.
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Materials and Methods
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Of 513 primary lung carcinoma cases diagnosed at the Kartal Education and Research Hospital Chest Diseases Clinic between January 1, 2001, and December 31, 2003, files of 322 patients (62.7%) who underwent bronchoscopy were reviewed. It was found that 290 patients had endobronchial lesions, and 115 patients in whom TBNA was performed in combination with CDT (FB plus BB plus BW) are reported in this study. All patients underwent chest radiography and CT of the chest. Probable locations for needle aspiration were determined prior to bronchoscopy by guidance of CT findings such as mediastinal or hilar lymphadenopathies or mass lesions.
Fiberoptic bronchoscopy was performed by four experienced bronchoscopists in patients receiving topical anesthesia in the supine position through the nasal or oral cavities (Olympus Co; Tokyo, Japan; Types T20D [n = 104] or BF 30 [n = 11]). The decision of TBNA application was made by each bronchoscopist during the procedure. The endobronchial lesions were classified into three groups; EML, submucosal disease, and peribronchial disease. Submucosal disease was defined as erythema, vascular flares, enhanced rugal pattern, thickening or loss of mucosal markings, and bronchial narrowing.7 Peribronchial disease was defined as luminal narrowing due to extrinsic compression by tumor or lymphadenomegaly. In order to avoid contamination, TBNA was performed out prior to other procedures such as BB, BW, and FB. A Wang transbronchial cytology needle (Mill Rose Laboratories; Mentor, OH; MW122 [n = 63] or MW522 [n = 52]) was used for TBNA. The transbronchial needle was introduced into the bronchoscope with the needle inside the metal hub while visualizing the trachea through the scope. When the metal hub was visible, the needle was advanced. In the presence of peribronchial disease, the needle was inserted into the lesion according to the "pushing" technique introduced by Wang.8 In exophitic mass lesions (EMLs), the needle was penetrated into the mass directly. In patients with submucosal disease, the needle was inserted at a 45° angle into the puncture site. One cytologic sample consisted of at least three subsequent aspirations from the same region, penetrating the bronchial wall in an area < 2 cm2. A 50-mL syringe was used to apply suction, and it was detached before retraction of the needle in order to avoid contamination. The aspirated material was blown into four or five slides, smeared, fixed with 95% alcohol, and sent for cytologic examination to the pathology department. On-site cytopathologic assessment was not performed, and fluoroscopy was not used during operation. Results of cytologic analysis were considered positive only when a sufficient number of definitely malignant cells were observed. All specimens having cellular atypia and abnormal cells highly suggestive of malignancy were considered negative. After the TBNA procedure, CDT such as FB (at least three times), BW, and BB were applied.
The diagnostic yield from TBNA, CDT, and TBNA plus CDT were evaluated according to the type of the endobronchial lesion, histologic subtypes, location of endobronchial lesion, and type of the needle. Mann-Whitney U, McNemar,
2, and Fisher exact tests were used for statistical analysis, and p < 0.05 was considered statistically significant.
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Results
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We reviewed files of 513 primary lung carcinoma cases diagnosed in our clinic in a 3-year period. Bronchoscopy was performed in 322 patients. Of these, 290 patients had EMLs, submucosal disease, or peribronchial disease, and TBNA and CDT were applied in 115 cases, which constituted the study population.
The group consisted of 98 male and 17 female patients (mean age, 52.5 ± 10.6 years [± SD]). Histopathologic diagnosis was non-small cell lung cancer (NSCLC) in 77 patients (67%) and small cell lung cancer (SCLC) in 38 patients (33%). In 105 patients (91%), histology findings were confirmed via bronchoscopy, and in 10 patients via transthoracic fine-needle aspiration. Bronchoscopically, 13 patients (11%) had EMLs, 32 patients (28%) had submucosal disease, and 70 patients (61%) had peribronchial disease. Diagnosis was made by CDT in 75 of 115 patients (65%). The addition of TBNA to CDT enabled histopathologic diagnosis in another 30 patients (26%) [Fig 1
] and improved the sensitivity of bronchoscopy from 65 to 91% (p < 0.001). If the sensitivities of CDT, TBNA, and CDT plus TBNA were compared for the different endobronchial lesion types, the addition of TBNA to CDT increased sensitivity in all lesion types, and this increase was statistically significant in the peribronchial disease group (p < 0.001) [Table 1
]. In the peribronchial disease group, diagnosis was made solely by TBNA in 24 patients (34.3% of the peribronchial disease group). When the 102 submucosal and peribronchial diseases were considered, the addition of TBNA to CDT increased the diagnostic yield from 63 to 90% and the difference was highly significant (p < 0.001; Table 1). TBNA was performed using a Mill Rose MW122 cytology needle in 63 patients and a Mill Rose MW522 cytology needle in 52 patients. Cases in these two groups had similar characteristics due to age, gender, type of endobronchial lesion, histologic type of tumor (p > 0.05); diagnostic yield of TBNA was 79.3% and 78.8%, respectively. The difference was statistically insignificant (p > 0.05).
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Table 1.. Diagnostic Yield of TBNA, CDT, and the Combination of These Techniques With Respect to the Type of Lesion*
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With respect to histologic subtypes (Table 2
), an increment from 74 to 100% was observed in diagnostic yield in SCLC when TBNA was combined with CDT (p = 0.002). The diagnostic efficacy improved from 57 to 100% by the addition of TBNA to CDT in the peribronchial disease group for SCLC (p = 0.031). Similarly, in the NSCLC group, the diagnosis was made by CDT in 47 of 77 patients (61%), and the diagnosis was made by CDT plus TBNA in 67 patients (87%) [p < 0.001]. In the NSCLC group, the best additional benefit from the addition of TBNA was obtained in the peribronchial disease group, with 84% sensitivity compared to 52% sensitivity of application of CDT alone (p < 0.001). For both histologic types, the addition of TBNA to CDT had an insignificant impact on the diagnostic yield for EML and submucosal disease.
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Table 2.. Diagnostic Yield of TBNA, CDT, and the Combination of These Techniques With Respect to the Histologic Subset*
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The diagnostic utility of TBNA, CDT, and CDT plus TBNA according to the location of endobronchial lesions was investigated (Table 3 ). The lesions were in the trachea or main bronchi in 34 patients (29%), in upper lobes in 50 patients (43%), in the right middle lobe in 22 patients (19%), and in the lower lobes in 9 patients (8%). The addition of TBNA to CDT increased the diagnostic yield irrespective of the location of the lesion, and this increase was significant in trachea and main bronchi, or the bronchi of the upper lobes and right middle lobe. When the right and left upper lobes were compared, this significance was attributed to right upper lobe lesions rather than left upper lobe lesions. Right- or left-sided malignant lesions demonstrated no difference due to diagnostic efficacy. Severe complications such as major bleeding and pneumothorax were not observed. Minor bleeding, when occurred, stopped spontaneously.
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Table 3.. Diagnostic Yield of TBNA, CDT, and the Combination of These Techniques With Respect to the Localization of the Lesion*
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Discussion
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TBNA has been widely studied for its role in the staging of lung carcinoma. Keeping the high false-positive rate of CT scans in mind, it is particularly recommended as an alternative method to mediastinoscopy in patients with radiologically enlarged mediastinal lymph nodes.9 Several studies5671011 indicate that the addition of this technique to CDT increases the diagnostic yield of bronchoscopy. Siddiqui et al12 reported 69.2% sensitivity and 100% specificity of TBNA in malignant endobronchial lesions. Dasgupta et al,7 in a prospective study including 55 patients, had positive results in 47 patients (85%) with TBNA and in 42 patients (76%) with CDT; diagnosis was made solely by TBNA in 11 patients (20%), and the addition of CDT contributed to a further increment in yield (96%). In another study,10 it was reported that 14% of 43 cases were diagnosed by TBNA alone and the combination of TBNA and CDT increased sensitivity from 65 to 79%. Consistent with these findings, Gullon et al5 observed that the addition of TBNA to CDT increased diagnostic yield significantly in endobronchial lesions for all lesion types. The combination of diagnostic tools was cost-effective for all lesion types; however, savings were significant only in the peribronchial disease group.
In our series including 115 patients, diagnosis was obtained in 65% by CDT, 79% by TBNA, and 91% by TBNA plus CDT. Twenty-four of 30 cases diagnosed by TBNA alone were in the peribronchial disease group (34.3% of the peribronchial disease group) [Fig 1]. The addition of TBNA to CDT increased sensitivity significantly only in this group. These findings seem to correlate with the reports of Gullon et al5 on cost-effectiveness, although no cost analysis was carried out for our study. FB had a diagnostic value of 67 to 100% in lung cancer cases with EML. Inadequate tissue sampling due to the presence of necrosis, a blood clot on the lesion, or formation of crush artifacts by FB make TBNA an indispensable tool in these lesions.67101213 Considering EML, Dasgupta et al7 reported 72% sensitivity with FB, 78% with TBNA, 84% with CDT, 97% with TBNA plus CDT, and the increase in sensitivity by addition of TBNA to CDT was not significant. These findings were confirmed by Bilaceroglu et al,14 who found that the rates of diagnosis for EML were 88% with FB and 94% with TBNA. Contradicting previous analyses, Karahalli et al15 reported that FB had the highest diagnostic rate in EMLs, and no additional benefit was detected with combination of TBNA and FB. In our study, in 13 patients with EML, the addition of TBNA to CDT increased sensitivity, without a statistically significant difference. Unlike EML, the diagnostic yield of CDT was low in submucosal and peribronchial diseases, where the mucosa was generally intact. TBNA enables penetration into the submucosa and access to the tumor through the bronchus wall in peribronchial disease, and usually diagnosis is available solely by TBNA.71013 Khoo et al1 reported that sensitivity of TBNA was 89% in submucosal disease and 83% in peribronchial disease. In the study of Shure and Fedullo,6 the sensitivity of FB was 55% for submucosal disease and peribronchial disease and that of TBNA was 71%, with the difference being insignificant. Addition of TBNA to FB increased the diagnostic rate to 89%, and this rise was statistically significant.6 In two different analyses, Dasgupta et al7 and Govert et al 11 found the combination of TBNA and CDT to have increased sensitivity compared to CDT alone. In contrast, Karahalli et al15 and Lundgren et al16 reported that TBNA had a lower diagnostic yield than FB in submucosal disease.1516 In our series, when submucosal and peribronchial diseases were considered together, the diagnostic yield was 63% with CDT, 78% with TBNA, and 90% with the combination of both. As a result, the addition of TBNA to CDT made a significant increase in the diagnostic rate. If submucosal and peribronchial diseases were considered separately, by addition of TBNA to CDT, sensitivity increased from 84 to 97% in submucosal disease without a statistical significant difference. In peribronchial disease, the diagnostic rate was 52% by CDT, 87% by TBNA plus CDT, and the superiority of combination over CDT was significant (p < 0.001).
When histologic subtypes are analyzed, the addition of TBNA to CDT increased sensitivity from 74 to 100% in SCLC patients. Similarly, in NSCLC, sensitivity increased from 61 to 87% by the combination of two techniques, and differences were significant. In both groups, the increases in sensitivity were due to peribronchial disease. Schenk et al4 had the best diagnostic rate with TBNA in SCLC (55%), and the lowest rate was in adenocarcinoma (35%). The investigators attributed this difference to increased cell count per volume in SCLC and its more central location compared to adenocarcinoma. In our series, the sensitivity of TBNA was 74% in NSCLC and 89% in SCLC, without a significant difference.
FB may be difficult to perform in upper lobe lesions, particularly if they are distally located. Buirski et al17 reported that FB had a lower diagnostic yield than TBNA in lesions located distal to the upper lobe orifice (36% vs 91%). In our study, it was concluded that the diagnostic yield of TBNA was higher than that of CDT in all locations (excluding lower lobes), but the difference was not statistically significant. When CDT and CDT plus TBNA were compared, the sensitivity of CDT plus TBNA was significantly higher than that of CDT in the trachea and main bronchi, upper lobes, and right middle lobe lesions. Haponik et al2 reported, in a study of 185 patients, that 38 of 61 positive results were on the right side, and the diagnostic rate of TBNA in right-sided lesions was significantly higher. In our study, no such correlation was found. No major complication due to TBNA of endobronchial lesions was reported in the literature,4671018 which is consistent with our findings.
In conclusion, in the diagnosis of malignant endobronchial lesions, TBNA is a sensitive and reliable but still underutilized method. Especially in cases of peribronchial disease, where CDT has low sensitivity, bronchoscopy remains inadequate and patients need to undergo more invasive and expensive procedures such as transthoracic fine-needle aspiration, mediastinoscopy, open-lung biopsy, or thoracoscopic biopsy. The addition of TBNA significantly increases the diagnostic yield of bronchoscopy for endobronchial lung cancer, especially if located in the trachea and main bronchi, upper lobes, and right middle lobe, and diminishes the need for more invasive surgical procedures.
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Footnotes
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Abbreviations: BB = bronchial brushing; BW = bronchial washing; CDT = conventional diagnostic techniques; EML = exophitic mass lesion; FB = forceps biopsy; NSCLC = non-small cell lung cancer; SCLC = small cell lung cancer; TBNA = transbronchial needle aspiration
Received for publication June 4, 2004.
Accepted for publication January 12, 2005.
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